Nasal Immunization with P. gingivalis Surface Protein Antigen and Cholera Toxin Adjuvant Induces T Helper 2 Responses in Both Mucosal and Systemic Compartments

Abstract

It is well establishedthat Porphyromonas gingivalisis one of the major pathogens of adult periodontitis. P. gingivalis produces an outer membrane protein with a molecular mass of 40-kDa (40k-OMP). In the present study, in order to assess the potential for application of 40k-OMP in the development of an antiperiodontal disease vaccine, we analyzed 40k-OMP-specific CD4+ T helper (Th) cell responses induced in the mucosal as well as systemic compartments when 40k-OMP was administered nasally. When CD4+T cells that were isolated from cervical lymph nodes (CLN) and spleens of mice immunized with 40k-OMP plus cholera toxin (CT) as adjuvant were re-stimulated with 40k-OMP in vitro, significant levels of proliferative responses were induced. In contrast, essentially no increased proliferation occurred in CLN and spleens taken from mice given 40k-OMP alone. Analysis of T helper (Th) 1 (IFN-y) and Th2 (IL-4, IL-5 and IL-6) cytokine responses showed that 40k-OMP-specific Th cells from both CLN and the spleen produced significant levels of IL-4, IL-5 and IL-6 but did not result in changes in IFN-y production. In contrast, marginal levels of IL-4, IL-5 and IL-6 production were seen in mice given 40k-OMP alone nasally. These results suggest that nasal administration of 40k-OMP plus CT as an adjuvant can elicit 40k-OMP-specific Th2-type cytokine responses in both mucosal and systemic compartments. Further, the nasal 40k-OMP vaccine possesses the potential for antiperiodontal vaccine.

Transcutaneous immunization with an outer membrane protein of Porphyromonas gingivalis without adjuvant elicits marked antibody responses

“…Normally, protein antigen given via the mucosal route without adjuvant has been generally reported to be only a weak immunogen (28, 45–47) and therefore, has been presumed to require a mucosal adjuvant such as CT to induce antigen‐specific antibody responses (28, 31, 45, 47). Our previous findings also indicated that nasal delivery of 40k‐OMP with CT as an adjuvant induced 40k‐OMP‐specific Th2‐type responses that in turn led to the induction of serum IgG and IgA as well as salivary IgA antibodies (30, 31). Despite its efficacy, however, CT is unsuitable for use in humans because it causes severe diarrhea (37).…”

“…Since mucosal (e.g. nasal or oral) administration of CT with soluble protein has proven to be an effective regimen for the generation of antigen‐specific antibody responses (20, 28, 30, 45, 47), we next examined the effect of the transcutaneous administration of CT as adjuvant on 40 K‐OMP‐specific antibody responses. Rats transcutaneously immunized with 40k‐OMP plus CT showed almost the same 40k‐OMP‐specific serum IgG and IgA responses as those immunized with 40k‐OMP alone (Fig.…”

The activity of polyclonal IgY derived from Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis in inhibiting colonization of Fusobacterium nucleatum and Streptococcus sanguinis

“…18 P. gingivalis and F. nucleatum have an outer membrane protein with a molecular mass of 40-kDa. 19 Against this background, the research aim was to determine whether IgY anti A. actinomycetemcomitans and P. gingivalis can be employed to inhibit colonization of F. nucleatum and S. sanguinis bacteria.…”